Prolonged social isolation of certain species of non-human primates and rats during early development has significant and long-lasting effects on behavior. We have available a population of 17-22 year old rhesus monkeys who were socially isolated during all or most of their first year of life. Preliminary data demonstrate that this social isolation caused profound and permanent effects on the behavior of these monkeys. We propose to study the neurobiology underlying these long-term changes in both rhesus monkeys, and in rats that will be socially isolated during either the pre- or post-weaning period of development. Because other preliminary data indicate that significant changes in dopaminergic function exist in these monkeys, one thrust will be characterize changes in central dopaminergic and other monoaminergic pathways using behavioral, pharmacological and biochemical methods. Initial studies will examine how selected drugs targeted at specific receptor populations alter certain isolation-induced behaviors, including stereotyped behavior, self- aggression, polydipsia, etc. Following two years of behavioral and psychopharmacological studies, the monkeys will be sacrificed, and in vitro experiments will be conducted on post-mortem brain tissue. Neurochemical and receptor binding studies will be performed in microdissected nuclei, and alterations in the density and affinity of several populations of monoamine receptors, and the concentration of monoamines and their acidic metabolities in specific brain regions will be measured. While these studies are being conducted in monkeys, related experiments will be ongoing in Sprague-Dawley rats. These experiments will not only permit comparison across geni, but also allow the preliminary testing of other hypotheses that may be relevant to the studies in rhesus monkeys. Finally, although existing data support the initial focus on dopaminergic transmission, the in vivo and in vitro methodologies to be used will allow us to determine alterations in monaminergic and other neuronal systems attributable to early social isolation, and careful archiving of tissue will permit its use for other post hoc hypotheses.